Hetero-Diels-Alder reaction alkyl

In a combined experimental and theoretical investigation it was found that the / -alkyl group in the dienophile gave a steric interaction in the transition-state structure which supported the asynchronous transition-state structure for the Lewis acid-catalyzed carbo- and hetero-Diels-Alder reactions. The calculated transition-state energies were of similar magnitude as obtained in other studies of these BF3-catalyzed carbo-Diels-Alder reactions. 

Optically active /3-ketoiminato cobalt(III) compounds based on chiral substituted ethylenedi-amine find use as efficient catalysts for the enatioselective hetero Diels Alder reaction of both aryl and alkyl aldehydes with l-methoxy-(3-(t-butyldimethylsilyl)oxy)-1,3-butadiene.1381 Cobalt(II) compounds of the same class of ligands promote enantioselective borohydride reduction of ketones, imines, and a,/3-unsaturated carboxylates.1382... 

Alkyl and silyl nitronates are, in principle, /V-alkoxy and /V-silyloxynitrones, and they can react with alkenes in 1,3-dipolar cycloadditions to form /V-alkoxy- or /V-silyloxyisoxaz.olidine (see Scheme 8.25). The alkoxy and silyloxy groups can be eliminated from the adduct on heating or by acid treatment to form 2-isoxazolines. It should be noticed that isoxazolines are also obtained by the reaction of nitrile oxides with alkenes thus, nitronates can be considered as synthetic equivalents of nitrile oxides. Since the pioneering work by Torssell et al. on the development of silyl nitronates, this type of reaction has become a useful synthetic tool. Recent development for generation of cyclic nitronates by hetero Diels-Alder reactions of nitroalkenes is discussed in Section 8.3. 

Similarly, Motorina described the intramolecular hetero-Diels-Alder reaction of N-alkyl-2-cyano-l-azadienes 86 (Scheme 9.26) [76] although the reaction had already been performed by heating the reactants in benzene overnight in a sealed tube at 110 °C, it was found that reaction time could be reduced to 14 min in a microwave oven at 650 W. 

Li et al.39 reported the hetero Diels-Alder reaction of alkyl-3-(t-butyldimethylsilyl) oxy-1,3-butadiene 95 with ethyl glyoxylate 96 in the presence of a salen-Co(II) catalyst 94 (2 mol%). Product 97 was obtained in 75% isolated yield with an endo. exo ratio >99 1. The enantiomeric excess of the endo-iorm was up to 52% (Scheme 5-30). 

Scheme 22. Effect of the enol ether alkyl group in the catalyzed hetero-Diels-Alder reaction. [Adapted from (221).]...

Ab initio calculations on aza-Diels-Alder reactions of electron-deficient imines with buta-l,3-diene show that these reactions are HOMO (diene)-LUMO(dienophile)-controlled and that electron-deficient imines should be more reactive than alkyl-or aryl-imines. The Diels-Alder reaction of r-butyl 2//-azirine-3-carboxylate (80) proceeds with high diastereoselectivity with electron-rich dienes (81) (Scheme 28). The hetero-Diels-Alder additions of imines with sterically demanding dienes yield perhydroquinolines bearing an angular methyl group. The asymmetric hetero-Diels-Alder reaction between alkenyloxazolines and isocyanates produces diastereometri-cally pure oxazolo[3,2-c]pyrimidines. °... 

The inverse type hetero-Diels-Alder reaction of functionally substituted a, p-unsaturated carbonyl compounds was also possible with -alkyl substituted enol ethers (Scheme 9) (25). This was demonstrated in the synthesis... 

Activated dienes such as Danishefsky s diene 112 can also be used in the hetero-Diels-Alder reaction with alkyl glyoxylates. Ghosh and co-workers showed that this reaction proceeded to form cycloadducts 113a,b in yields up to 76% and ee up to 70% using either bu-box 3, phe-box 6 or inda-box ent-9a. The results are summarized in Table 9.18 (Fig. 9.36). 

Aminoindanol-derived Schiff bases were developed as tridentate ligands for the chromium-catalyzed hetero Diels-Alder reaction between weakly nucleophilic dienes and unactivated aldehydes.24 The generality of the utility of these Schiff bases, readily obtained by condensation of 1 with the corresponding aldehyde, was later demonstrated in the hetero Diels-Alder reaction between Danishefsky s diene and chiral aldehydes,25 in the inverse electron-demand hetero Diels-Alder reaction of a,P-unsaturated aldehydes with alkyl vinyl ethers,26 and in hetero-ene reactions.27... 

Chromium complex 53 was also shown to efficiently catalyze the inverse electron-demand hetero Diels-Alder reaction of a,(3-unsaturated aldehydes with alkyl vinyl ethers (Scheme 17.19).26 Although the uncatalyzed process required elevated temperatures and pressures to give dihydropyrans in good yields but poor endo. exo selectivities, the reaction proceeded at room temperature in the presence of 5 mol% of ent-53 and 4A molecular sieves in dichloromethane of tert-butyl methyl ether with excellent diastereoselectivity (endo. exo >96 4) and promising enantioselectivities (72-78% ee). Optimal results were achieved using a solvent-free system and excess vinyl ether. 

Recently, Breitmaier et al. [94] showed that in the hetero Diels-Alder reaction of triketones such as indantrione 2-34 and alloxane with the chiral 2-methyl-1-(1-phenylalkoxy)-1,3-butadienes 2-35 a good diastereoselectivity can be obtained. The cycloaddition proceeded regioselectively with increasing facial selectivity in correlation to the steric demand of the alkyl group at the benzylic position in the auxiliary to give the dihydropyran 2-36 as the major and 2-37 as the minor product (Fig. 2-10). 

Azo compounds like esters or imides of azo dicarboxylic acid act as reactive dienophiles in normal electron demand hetero Diels-Alder reactions due to the strong activation caused by two electron-withdrawing moieties. In the last years, considerable attention has focused on alkyl and phenyl derivatives of 1,2,4-tria-zoline-3,5-diones since their cycloadditions to chiral dienes proceed with often excellent facial selectivities. Thus, when reacting an oxapropellane derived diene with N -methyltriazolinedione, Paquette et al. obtained the cycloadduct as single diastereomer, but both maleic anhydride and N-phenyl maleimide were distinctly less reactive and turned out to undergo cycloadditions with poor selectivities [289]. 

The quinodimethane linker 1.39 (97) was easily prepared from hydroxymethyl PS resin and anthranilic acid this linker can be used to perform hetero-Diels-Alder reactions to form condensed six-member heterocycles. Cleavage with Lewis acid-nucleophile cocktails in DCM for 16-24 h at rt produces unsubstituted or alkyl-substituted heterocycles in good yields. 

Activation of 3-alkyl and 3-phenyl-2H-aziiines by Lewis acids also promotes their participation in hetero Diels-Alder reactions with a variety of dienes. This methodology circumvents the previous requirement of needing an electron-withdrawing carboxyl moiety at the 3-position of the 2H-azirine ring (01TL9289). Thus, the reaction of 2H-azirine 125 with Danishefsky s diene gave the endo-cycloadduct 126... 

Inverse electron demand hetero-Diels-Alder reactions of acyl phosphonates or a-keto ester heterodienes and enol ethers are also catalyzed by (5, iS )-t-Bu-box complexes. High levels of enantioselectivity are obtained with y-alkyl-, -aryl-, -alkoxy-... 

Asymmetric Hetero Diels-Alder Reaction. In contrast to the CAB catalyst (2 R = H) which is stable and both air and moisture sensitive, the B-alkylated CAB catalyst (3 R = Ph or alkyl) is stable and can be stored in a closed container at rt. A solution of the CAB (3 R = Ph) catalyzes Diels-Alder, aldol, and Sakurai-Hosomi reactions. Although the asymmetric inductions achieved by these complexes are slightly less efficient than that of the corresponding hydride-type catalyst, the CAB catalyst (3 R = Ph) is shown to be an excellent system for hetero Diels-Alder reactions. 

The B-alkylated CAB catalyst (3) is easily prepared in situ by mixing a 1 1 molar ratio of tartaric acid derivative and phenyl-boronic acid in dry propionitrile at room temperature for 0.5 h. The hetero Diels-Alder reaction of aldehydes with Danishefsky dienes is promoted by 20 mol % of this catalyst solution at —78 °C for several hours to produce dihydropyranone derivatives of high optical purity (eq 9). 

We have developed a stable CAB 2 (R = aryl) complex that can be prepared in situ by mixing tartaric acid derivative and arylboronic acid at room temperature. In contrast with 2, R = H, which is both air- and moisture-sensitive, the B-alkylated catalyst 2, R = aryl or alkyl, is stable and can be stored in closed containers at room temperature (Eq. 39). A solution of the catalyst (20 mol %) is effective in catalyzing the hetero Diels-Alder reaction of aldehydes with a Danishefsky diene to produce dihydro-pyrone derivatives of high optical purity (up to 98 % ee) (Eq. 40) [39]. The extent of asymmetric induction is largely dependent on the structure of the boronic acid. In general, bulky phenylboronic acid (R = 2,4,6-Me3CeH2, o-MeOC6H4) results in excellent asymmetric induction. 

Iron(III) 2-ethylhexanoate is a catalyst for the stereoselective hetero-Diels-Alder reaction of ethyl ( )-4-oxobutenoate with alkyl vinyl ethers to give ci5 -2-alkoxy-3,4-dihydro-2//-pyran-4-carboxylic acid ethyl esters with a high diastereoselectivity (Sch. 57) [203],... 

In contrast, the intermediately formed methylenecyclopropane 44 reacts with electron-rich alkenes to give cycloadducts, e.g. 45, with the bis(acceptor)methylenecyclopropane reacting as a heterodiene. This hetero-Diels-Alder reaction is also applicable to electron-rich alkynes, e.g. formation of 46. Thus, a solution of 3-acetoxy-5,5-dimethyl-2-(l-piperidinocyclo-propyl)cyclohexen-2-enone (47) and 1 equivalent of alkyne was reacted at 36°C for 4 hours. Alkyl-substituted alkynes, although applied in great excess, did not form any products. Depending on the substituents, further acidic hydrolysis opens up a method for the preparation of acetates or lactones. 

Dihydropyrans are useful intermediates in the total synthesis of monosaccharides and have been prepared by hetero-Diels-Alder reaction of simple alkyl- and arylaldehydes 48 with electron-rich ( )-l-methoxy-l,3-butadiene (49) in reasonable to good yield. As expected e do-diastereoselectivity is predominant because, as usual, pressure strongly favours e do-addition (Scheme 7.12). 

An important development in the hetero Diels-Alder reaction came when Jurczak used high pressure to help improve the reactivity of dienes with aldehydes. 1-Methoxybutadiene, for example, was shown to react at 15-25 kbar (I bar = l(X) kPa) with a variety of unactivated aldehydes. - These reactions give predominantly endo adducts and allow for the use of simple alkyl and aromatic aldehydes as dienophiles. Jurczak also realized the importance of this reaction in the synthesis of carbohydrates and applied it to the construction of simple monosaccharide derivatives (see Section 2.5.2. ). " ... 

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